Ryman-Rasmussen Jessica P, Tewksbury Earl W, Moss Owen R, Cesta Mark F, Wong Brian A, Bonner James C
North Carolina State University, Box 7633, Raleigh, NC 27695, USA.
Am J Respir Cell Mol Biol. 2009 Mar;40(3):349-58. doi: 10.1165/rcmb.2008-0276OC. Epub 2008 Sep 11.
Carbon nanotubes are gaining increasing attention due to possible health risks from occupational or environmental exposures. This study tested the hypothesis that inhaled multiwalled carbon nanotubes (MWCNT) would increase airway fibrosis in mice with allergic asthma. Normal and ovalbumin-sensitized mice were exposed to a MWCNT aerosol (100 mg/m(3)) or saline aerosol for 6 hours. Lung injury, inflammation, and fibrosis were examined by histopathology, clinical chemistry, ELISA, or RT-PCR for cytokines/chemokines, growth factors, and collagen at 1 and 14 days after inhalation. Inhaled MWCNT were distributed throughout the lung and found in macrophages by light microscopy, but were also evident in epithelial cells by electron microscopy. Quantitative morphometry showed significant airway fibrosis at 14 days in mice that received a combination of ovalbumin and MWCNT, but not in mice that received ovalbumin or MWCNT only. Ovalbumin-sensitized mice that did not inhale MWCNT had elevated levels IL-13 and transforming growth factor (TGF)-beta1 in lung lavage fluid, but not platelet-derived growth factor (PDGF)-AA. In contrast, unsensitized mice that inhaled MWCNT had elevated PDGF-AA, but not increased levels of TGF-beta1 and IL-13. This suggested that airway fibrosis resulting from combined ovalbumin sensitization and MWCNT inhalation requires PDGF, a potent fibroblast mitogen, and TGF-beta1, which stimulates collagen production. Combined ovalbumin sensitization and MWCNT inhalation also synergistically increased IL-5 mRNA levels, which could further contribute to airway fibrosis. These data indicate that inhaled MWCNT require pre-existing inflammation to cause airway fibrosis. Our findings suggest that individuals with pre-existing allergic inflammation may be susceptible to airway fibrosis from inhaled MWCNT.
由于职业或环境暴露可能带来的健康风险，碳纳米管正受到越来越多的关注。本研究检验了以下假设：吸入多壁碳纳米管（MWCNT）会增加过敏性哮喘小鼠的气道纤维化。将正常小鼠和卵清蛋白致敏小鼠暴露于MWCNT气雾剂（100 mg/m(3)）或盐雾气溶胶中6小时。在吸入后1天和14天，通过组织病理学、临床化学、酶联免疫吸附测定（ELISA）或逆转录-聚合酶链反应（RT-PCR）检测细胞因子/趋化因子、生长因子和胶原蛋白，以评估肺损伤、炎症和纤维化情况。通过光学显微镜观察发现，吸入的MWCNT分布于整个肺部，并存在于巨噬细胞中，但通过电子显微镜也在上皮细胞中观察到其存在。定量形态学分析显示，在接受卵清蛋白和MWCNT联合处理的小鼠中，14天时出现了显著的气道纤维化，而仅接受卵清蛋白或MWCNT处理的小鼠则未出现。未吸入MWCNT的卵清蛋白致敏小鼠肺灌洗液中白细胞介素-13（IL-13）和转化生长因子（TGF）-β1水平升高，但血小板衍生生长因子（PDGF）-AA水平未升高。相反，吸入MWCNT的未致敏小鼠PDGF-AA水平升高，但TGF-β1和IL-13水平未升高。这表明，卵清蛋白致敏和MWCNT吸入联合导致的气道纤维化需要PDGF（一种强大的成纤维细胞有丝分裂原）和TGF-β1（刺激胶原蛋白产生）。卵清蛋白致敏和MWCNT吸入联合还协同增加了IL-5 mRNA水平，这可能进一步促进气道纤维化。这些数据表明，吸入的MWCNT需要预先存在的炎症才能导致气道纤维化。我们的研究结果表明，已有过敏性炎症的个体可能易受吸入MWCNT导致的气道纤维化影响。
